Analysis and implications of mutational variation

Abstract

Variation from new mutations is important for several questions in quantitative genetics. Key parameters are the genomic mutation rate and the distribution of effects of mutations (DEM), which determine the amount of new quantitative variation that arises per generation from mutation (V M ). Here, we review methods and empirical results concerning mutation accumulation (MA) experiments that have shed light on properties of mutations affecting quantitative traits. Surprisingly, most data on fitness traits from laboratory assays of MA lines indicate that the DEM is platykurtic in form (i.e., substantially less leptokurtic than an exponential distribution), and imply that most variation is produced by mutations of moderate to large effect. This finding contrasts with results from MA or mutagenesis experiments in which mutational changes to the DNA can be assayed directly, which imply that the vast majority of mutations have very small phenotypic effects, and that the distribution has a leptokurtic form. We compare these findings with recent approaches that attempt to infer the DEM for fitness based on comparing the frequency spectra of segregating nucleotide polymorphisms at putatively neutral and selected sites in population samples. When applied to data for humans and Drosophila, these analyses also indicate that the DEM is strongly leptokurtic. However, by combining the resultant estimates of parameters of the DEM with estimates of the mutation rate per nucleotide, the predicted V M for fitness is only a tiny fraction of V M observed in MA experiments. This discrepancy can be explained if we postulate that a few deleterious mutations of large effect contribute most of the mutational variation observed in MA experiments and that such mutations segregate at very low frequencies in natural populations, and effectively are never seen in population samples.

Causes of natural variation in fitness: Evidence from studies of Drosophila populations

“…There is thus a major discrepancy between the value of V M and the population genomics estimate of t. A similar conclusion was reached in ref. 7, using a somewhat different argument.…”

“…The most likely explanation for these inconsistencies between the population genomics and quantitative genetics approaches is that mutations with effects of the sizes estimated from the population genomics data are not the only contributors to D M and V M . There must be an additional source of mildly deleterious mutations, probably mainly involving transposable element (TE) insertions (7,54) and other types of large indels (12). These types of mutation are likely to have much larger effects on viability of their heterozygous carriers than most single nucleotide mutations or small indels, because they can completely disrupt sequences of functional importance; a minority of single nucleotide changes may also contribute to this class.…”

“…7. I largely confine myself to results from studies of the fruitfly Drosophila, because this has been the most useful model organism for investigating these problems, especially by quantitative genetics methods.…”

Rate and molecular spectrum of spontaneous mutations in the bacteriumEscherichia colias determined by whole-genome sequencing

“…The MA protocol is designed to allow mutations to occur in a neutral manner, devoid of selective pressure (5). The general strategy is to establish a number of clonal populations from a founder individual and then to take each population through repeated single-individual bottlenecks for thousands of generations.…”

Totipotencialidad en plántulas de aguacate en la resistencia a Phytophthora cinnamomi

“…Totipotent seedlings frequency was low because in nature occurs randomly and at low frequencies. To increase the frequency of new shoots of avocado embryonic axes uses the induction of growth hormones (cytokinins) (Mohamed et al, 1993;Keightley et al, 2009). Re inoculation ensures P. cinnamomi infection on new shoots, which was possible to prove in this research, because no statistically significant differences were found in the number of seedlings of Atlixco and Tepeyanco genotypes.…”